title: Plasma protein biosignatures for detection of cardiac allograft vasculopathy.
abstract: BACKGROUND
  Coronary angiography remains the most widely used tool for routine screening and diagnosis of cardiac allograft vasculopathy (CAV), a major pathologic process that develops in 50% of cardiac transplant recipients beyond the first year after transplant. Given the invasiveness, expense, discomfort, and risk of complications associated with angiography, a minimally invasive alternative that is sensitive and specific would be highly desirable for monitoring CAV in patients.
  
  
  METHODS
  Plasma proteomic analysis using isobaric tags for relative and absolute quantitation-matrix-assisted laser desorption ionization double time-of-flight mass spectrometry was carried out on samples from 40 cardiac transplant patients (10 CAV, 9 non-significant CAV, 21 possible CAV). Presence of CAV was defined as left anterior descending artery diameter stenosis ≥ 40% by digital angiography and quantitatively measured by blinded expert appraisal. Moderated t-test robust-linear models for microarray data were used to identify biomarkers that are significantly differentially expressed between patient samples with CAV and with non-significant CAV. A proteomic panel for diagnosis of CAV was generated using the Elastic Net classification method.
  
  
  RESULTS
  We identified an 18-plasma protein biomarker classifier panel that was able to classify and differentiate patients with angiographically significant CAV from those without significant CAV, with an 80% sensitivity and 89% specificity, while providing insight into the possible underlying immune and non-alloimmune contributory mechanisms of CAV.
  
  
  CONCLUSIONS
  Our results support of the potential utility of proteomic biomarker panels as a minimally invasive means to identify patients with significant, angiographically detectable coronary artery stenosis in the cardiac allograft, in the context of post-cardiac transplantation monitoring and screening for CAV. The potential biologic significance of the biomarkers identified may also help improve our understanding of CAV pathophysiology.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 2K5, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Lin
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cohen Freue
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.forename: G B
authors.initials: GB
authors.lastname: John Mancini
authors.forename: Mayu
authors.initials: M
authors.lastname: Sasaki
authors.forename: Alice
authors.initials: A
authors.lastname: Mui
authors.forename: Janet
authors.initials: J
authors.lastname: Wilson-McManus
authors.forename: Andrew
authors.initials: A
authors.lastname: Ignaszewski
authors.forename: Carol
authors.initials: C
authors.lastname: Imai
authors.forename: Anna
authors.initials: A
authors.lastname: Meredith
authors.forename: Robert
authors.initials: R
authors.lastname: Balshaw
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Ng
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keown
authors.forename: W
authors.initials: W
authors.lastname: Robert McMaster
authors.forename: Ron
authors.initials: R
authors.lastname: Carere
authors.forename: John G
authors.initials: JG
authors.lastname: Webb
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000097:blood* / Q000209:etiology*
chemical_list: D001798:Blood Proteins